Epinephrine synthesis by an N-methyltransferase in rat liver.
We investigated if liver can synthesize epinephrine in vitro and in vivo. Homogenates of rat liver readily synthesized [3H]epinephrine from [3H]S-adenosylmethionine and norepinephrine. Liver homogenates also N-methylated dopamine at more than twice the rate that they N-methylated norepinephrine. In contrast, adrenal homogenates, which N-methylate norepinephrine to form epinephrine using the enzyme phenylethanolamine-N-methyltransferase (PNMT), methylated dopamine only about 1% as well as norepinephrine. Synthesis of epinephrine by liver homogenates was not significantly inhibited by the PNMT inhibitor SKF 29661 at a concentration that inhibited adrenal homogenate epinephrine synthesis by nearly 90%. These findings indicate that liver can synthesize epinephrine in vitro using an enzyme other than PNMT. Adrenal demedullation of rats reduced plasma epinephrine levels to 7% of control values, but left liver epinephrine and epinephrine-forming enzyme levels unchanged. Treatment of demedullated rats with 6-hydroxydopamine plus reserpine also resulted in dramatically reduced plasma epinephrine levels but no change in hepatic epinephrine and N-methylating enzyme levels. We conclude that the liver synthesizes its own epinephrine.
Elayan
H
H
Department of Medicine, University of California San Diego Medical Center.
Kennedy
B
B
Ziegler
M G
MG
D000818:Animals; D004837:Epinephrine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008780:Methyltransferases; D010625:Phenylethanolamine N-Methyltransferase; D009638:Norepinephrine; D004837:Epinephrine